Scientists at the MPI CEC have introduced a catalytic approach that enables efficient access to important building blocks for pharmaceuticals and fine chemicals. Published in the prestigious Journal of the American Chemical Society, their work addresses a long-standing challenge: selectively hydrogenating complex heteroaromatic compounds (such as quinolines, indoles, and benzofurans) while preserving the aromaticity of the adjacent carbocycle. This precision is essential for creating high-value drug intermediates efficiently, yet conventional catalysts often fail to combine activity, selectivity, and stability. The team’s solution, ruthenium phosphide nanoparticles immobilized on a supported ionic liquid phase (Ru₅₀P₅₀@SILP), opens new pathways to sustainable chemical manufacturing.

Smart Design, Superior Performance

Unlike traditional methods requiring harsh conditions, the synthesis of RuₓP₁₀₀₋ₓ@SILP catalysts was achieved under mild temperatures (60 °C) and leveraged a molecularly-modified support to stabilize size-controlled nanoparticles (ca. 2 nm). Advanced characterization techniques and detailed catalytic study revealed the catalyst’s properties and superior performance. Remarkably, Ru₅₀P₅₀@SILP achieved the selective partial hydrogenation of a broad variety of bicyclic heterocycles (34 examples) while preserving sensitive functional groups including halogens, esters, and even bulky substituents.

From Lab Bench to Real-World Impact

The catalyst’s versatility shines in synthesizing high-value targets, demonstrating direct applications in drug development. For instance, it streamlined the production of cuspareine (an antiviral agent) and salsolidine (a neuroactive alkaloid), achieving high yields while minimizing waste. Crucially, it enabled deuterium labeling, a vital tool for improving solubility and pharmokinetic activities. Beyond batch processes, the team led by Dr. Alexis Bordet showcased seamless scalability in continuous flow reactors, maintaining stability for over 7 hours with a space-time yield of 0.4 kg/L·h. This efficiency, combined with tolerance toward challenging substrates like benzothiophenes, positions the technology as a versatile platform for industrial catalysis.

Pioneering Greener Chemistry

“In this work, we leveraged our  recently-reported low temperature synthetic route to metal phosphides to develop a new catalytic system with tailor-made reactivity for a challenging transformation.” emphasizes Hooman Ghazi Zahedi, first author of the study. The achievement, however, is a collective effort: A team of 10 scientists from three departments at MPI CEC, including the groups of Walter Leitner and Alexis Bordet (corresponding authors), alongside expertise in X-ray spectroscopy (Serena DeBeer) and NMR analytics (Thomas Wiegand). By combining synthetic innovation with state-of-the-art characterization, the team established a sustainable and robust catalytic system. "Importantly, this methodology allowed us to access drug molecules of high significance in an efficient and environmentally benign manner.”, notes Zahedi. Overall, this work paves the way for scalable and sustainable syntheses in pharmaceutical and fine chemical manufacturing.

Original Paper:

Hooman Ghazi Zahedi, Jannis Hertel, Bhaskar Paul, Liqun Kang, Jacob Johny, Yufei Wu, Thomas Wiegand, Serena DeBeer, Walter Leitner, and Alexis Bordet (2026). Selective Hydrogenation of Heteroarenes Using Supported Ruthenium Phosphide Nanoparticle Catalysts Journal of the American Chemical Society. ASAP. DOI: 10.1021/jacs.5c16144 https://pubs.acs.org/doi/full/10.1021/jacs.5c16144 

Recently-reported synthetic route:

Sodreau, A., Zahedi, H. G., Dervişoğlu, R., Kang, L., Menten, J., Zenner, J., Terefenko, N., DeBeer, S., Wiegand, T., Bordet, A., Leitner, W. A Simple and Versatile Approach for the Low-Temperature Synthesis of Transition Metal Phosphide Nanoparticles from Metal Chloride Complexes and P(SiMe₃)₃. Adv. Mater. 2023, 2306621. https://doi.org/10.1002/adma.202306621